Endocrine Abstracts

Background: Kisspeptin-54 (KP54) stimulates hypothalamic GnRH release. The kisspeptin analogue, MVT-602, has a longer half-life (t1/2108min) than KP54 (t1/228mins). MVT-602 potently stimulates gonadotrophin release in men. We sought to determine for the first time the effect of MVT-602 on gonadotrophin release in healthy women.Methods: A two-phase dose-finding study was carried out in 9 healthy women, 18–35 yrs with regular men...

Introduction: Angiopoietin-like proteins (ANGPTLs) are a family of 8 glycoproteins with pleiotropic effects in metabolism, angiogenesis, inflammation and cancer. ANGPTL3, 4 and 8 play major roles in regulating lipid levels, via inhibition of lipoprotein lipase. Increased serum ANGPTL3, 4, 8 levels are associated with obesity, diabetes, metabolic syndrome and fatty liver. Furthermore, cord blood ANGPTL8 is higher than in maternal serum, suggesting a role in fetal development an...

Background: PRRT, licensed for gastroenteropancreatic (GEP) NETs, has been used with somatostatin analogues such as lanreotide autogel (LAN). PRELUDE is the first international, multicentre retrospective study, with central radiology reading, to describe use of LAN with PRRT (LAN-PRRT) in advanced NETs.Methods: PRELUDE (NCT02788578) was an international, retrospective, non-comparative analysis of medical records of patients receiving LAN with 177Lu-DOTAT...

Background: Placentation (invasion of the placenta into the maternal endometrium of pregnancy known as the decidua) is hypothesised to be critical for healthy placental function and is abnormal in two thirds of miscarriage. Kisspeptin has emerged as a putative regulator of physiological placentation; it is highly expressed in placental syncitio-trophoblasts, whereas its receptor is expressed in both syncitio- and cyto-trophoblasts, such that kisspeptin is hypothesized to play ...

Background: Patients with acromegaly responding to injectable somatostatin receptor ligands (SRL) are often treated for decades without deterioration of biochemical response (except for routine fluctuations in IGF-I control), unless there are changing clinical circumstances such as persistent or recurrent tumor growth. Oral octreotide capsules (OOC) have been formulated as a potential therapy for acromegaly and the safety and efficacy was evaluated in the CHIASMA OPTIMAL pivot...

Background: Hypogonadotrophic hypogonadism is characterised by hypogonadism in the context of low/inappropriately normal gonadotrophin levels. Congenital Hypogonadotrophic Hypogonadism (CHH) occurs due to disrupted GnRH neuronal migration, or impaired hypothalamic GnRH secretion or action. However, no direct test of hypothalamic GnRH neuronal function currently exists. Kisspeptin-54 is a neuropeptide that stimulates endogenous hypothalamic GnRH release. Thus, we investigated w...

Background: Most patients responding to injectable somatostatin receptor ligands exhibit IGF-I variability around the upper limit of normal (ULN) during long-term follow up. These fluctuations are thought to result from assay variability, nutrition, comorbid conditions, concomitant medications and other unknown factors. The magnitude and factors affecting this variability arenot well understood in patients with acromegaly treated with injectable SRLs.Met...

Background: Distinguishing non-specific signs/symptoms of acromegaly from treatment-emergent adverse events (TEAEs) in patients treated with somatostatin receptor ligands has proven difficult given limited data from placebo-controlled studies. The CHIASMA OPTIMALstudy provides a novel data set to evaluate the incidence of adverse events (AEs) in patients randomized to oral octreotide capsules (OOC) or placebo.Methods: A multinational, randomized, placebo...

Background: Data on the impact of withdrawal from long-acting somatostatin receptor ligand (SRL) injections on disease activity in patients with acromegaly are limited. The CHIASMA OPTIMAL study assessed the efficacy and safety of oral octreotide capsules (OOC) in adult patients with acromegaly responding to SRL injections. The placebo arm of this study allowed for assessment of acromegaly activity in patients after withdrawal from SRL treatment.Methods:...

Objective: The phase 3 CHIASMA OPTIMAL study assessed efficacy and safety of oral octreotide capsules (OOC) in patients with acromegaly controlled on injectable somatostatin receptor ligands (SRLs). Sensitivity analyses were conducted for efficacy endpoints using two methods of imputation (i.e., the process of replacing clinical data with substitution values) to address missing data points due to some subjects reverting back to their prior injectable SRL treatment.<p class...